title: Exercise preconditioning provides long-term protection against early chronic doxorubicin cardiotoxicity.
abstract: Acute doxorubicin (DOX) cardiotoxicity can be attenuated by exercise preconditioning, but little is known of whether this cardioprotection continues beyond 10 days post-DOX administration. The purpose of this study was to determine the effects of exercise preconditioning on early chronic DOX-induced cardiotoxicity. Male rats were randomly assigned to sedentary, treadmill, or wheel running groups. Treadmill and wheel running animals participated in a progressive treadmill training protocol or voluntary wheel running, respectively, for 10 weeks. Following the intervention, animals were further randomized to receive either DOX (sedentary + DOX, treadmill + DOX, wheel running + DOX) or saline (sedentary + saline, treadmill + saline, wheel running + saline). All animals then remained sedentary for 4 weeks. A 22% reduction in fractional shortening was observed in left ventricles from previously sedentary animals receiving DOX when compared with sedentary + saline. This degree of decline was not observed in treadmill + DOX and wheel running + DOX. Sedentary + DOX possessed significantly depressed mitral and aortic valve blood flow velocities when compared with sedentary + saline, but these decrements were not observed in treadmill + DOX and wheel running + DOX. Ex vivo analysis revealed that left ventricular developed pressure and maximal rate of pressure development were significantly lower in sedentary + DOX when compared to sedentary + saline. Treadmill and wheel running prior to DOX treatment protected against these decrements. Exercise cardioprotection was associated with preserved myosin heavy chain but not sarcoendoplasmic reticulum Ca(2+) ATPase 2a expression. In conclusion, 10 weeks of prior exercise protected against early chronic DOX cardiotoxicity suggesting that training status may be a determining factor in the degree of late-onset cardiotoxicity experienced by cancer patients undergoing treatment with DOX.
authors.affiliation: University of Northern Colorado, Greeley, CO 80639, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Hydock
authors.forename: Chia-Ying
authors.initials: CY
authors.lastname: Lien
authors.forename: Brock T
authors.initials: BT
authors.lastname: Jensen
authors.forename: Carole M
authors.initials: CM
authors.lastname: Schneider
authors.forename: Reid
authors.initials: R
authors.lastname: Hayward
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D004317:Doxorubicin / Q000633:toxicity*; D004452:Echocardiography; D006321:Heart / Q000187:drug effects* / Q000502:physiology*; D006331:Heart Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D008297:Male; D018995:Myosin Heavy Chains; D010805:Physical Conditioning, Animal / Q000502:physiology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000096:biosynthesis / Q000235:genetics; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D000903:Antibiotics, Antineoplastic; C506948:Atp2a2 protein, rat; D004317:Doxorubicin; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D018995:Myosin Heavy Chains